Since the discovery of DNA, there has been a concerted effort to develop ways to actually experimentally determine the sequences of the constitutive chemical bases. The first method for systematically sequencing DNA was introduced by Sanger in 1978.
This basic method was automated in a commercial instrument platform in the late 1980's, enabling the sequencing of the first human genome. The success of this effort motivated the development of a number of “massively parallel” sequencing platforms, with the goal of dramatically reducing the cost and time required to sequence a human genome. These automated methods generally rely on processing millions to billions of sequencing reactions at the same time, in highly miniaturized microfluidic formats.
Although a variety of other related techniques and commercial platforms followed, further improvements in quality and accuracy of sequencing, as well as reductions in cost and time, remain highly desirable. This is especially true to make genome sequencing practical for widespread use in precision medicine, where it is desirable to sequence the genomes of millions of individuals with a clinical grade of quality. Further, many DNA sequencing techniques utilize optical means with fluorescence reporters. Such methods can be cumbersome, slow in detection speed, and difficult to mass produce or make affordable. Label-free DNA or genome sequencing approaches would have the advantages of not having to use fluorescent type labeling processes and associated optical systems, and are thus particularly needed.